tbuckley/cabot-search huggingface dataset:
P104: Consolidation Therapy with Brentuximab Vedotin after Autologous Stem Cell Transplantation for Relapsed/Refractory Hodgkin Lymphoma in the Czech Republic.
Authors: Jozef Michalka, Jana Marková, Ľubica Gahérová, Mária Maco, Vít Procházka, Jan Kořen, Alice Sýkorová, Pavla Štěpánková, Kateřina Steinerová, Lekaa Mohammad, Juraj Ďuraš, Barbora Velacková, Tomáš Doležal, Kateřina Benešová, Marie Lukášová, Andrea Janíková, Zdeněk. Král., Heidi Móciková
Journal: HemaSphere (2022)

Figure 1: Progression-free survival figure, N=39 pts Introduction: Consolidation therapy with brentuximab vedotin (BV) following autologous stem cell transplantation (ASCT) has demonstrated improved progression-free survival (PFS) in high-risk patients (pts) with relapsed/refractory classic Hodgkin lymphoma (cHL) in the AETHERA trial. We have analysed data from seven centres of intensive haematological care in the Czech Republic between January 2015 and December 2021 based on real-life experience with the treatment. The primary goals included basic statistical decription, assessment of the PFS and toxicity of the treatment. Patients and Methods: All of the pts were treated with high-dose chemotherapy and ASCT in the first relapse, all had at least one of the risk factors as per AETHERA and no previous treatment with BV. We have analysed 39 pts treated with BV 1.8 mg/kg i.v. every 3 weeks for a maximum of 16 cycles. Results: Median age was 37 years (range 19–65) at the time of the first dose of BV. Nearly 80% of pts were initially treated as advanced stage cHL and eBEACOPP was administered in 59% of pts in the frontline setting. Primary refractory or early relapsed (within 12 months after the frontline therapy) cHL pts represented 69% of the analysed cohort. Two different salvage regimens were administered in 30.8% and failure to achieve a complete response (CR) after salvage chemotherapies prior ASCT was seen in 64% of pts. The median number of BV administered was 8 (1–16), with 16 completed cycles in 20.5% pts. Main reasons for early discontinuation were neuropathy and relapsed or progressive disease, both in 15.4%. Overall, 82% of pts achieved CR during the treatment. With a median follow-up 28 months the 2-year PFS was 66.2% (95% CI 0.52–0.85) and the 2-year overall survival was 95% (95% CI 0.82–1.00). Two pts died, one of progressive lymphoma and one of severe bacterial infection. Peripheral sensory neuropathy occurred in 38.5% (grade 3–4 in 10.3%), neutropenia in 28.2% (grade 3–4 in 17.9%) and respiratory infections in 28.5% (grade 3–4 in 2.6%). Discussion: Despite some differences in the analysed groups, our results are comparable with a few real-world data published lately and support the notion that BV consolidation improves PFS in patients with at least one risk factor for subsequent relapse of cHL and has a feasible and manageable toxicity. Supported by following grants MH CZ – DRO (FNOl, 00098892) AZV NU22-03-00182
P085: Epidemiology and results of the first line therapy of HIV-related Hodgkin Lymphoma: Russian retrospective multicenter study
Authors: Andrey Chekalov, Marina Popova, Ivan Tsygankov, Yuliya Rogacheva, Nikita Volkov, Anastasia Beynarovich, Kirill Lepik, Marina Demchenkova, Marina Grigorieva, Tatiana Schneider, Yuliya Kopeikina, Natalia Medvedeva, Ilya Zyuzgin, Elena Pavlyuchenko, Alexander Levanov, Alexander Myasnikov, Natalia Mikhailova, Vadim Baykov, Alexander Kulagin
Journal: HemaSphere (2022)

Background: Patients with HIV infection have a significantly higher risk of developing cancer comparing to general population. Hodgkin lymphoma (HL) is one of the most common non-AIDS-defining malignancies. Currently, there is no unified approach to the treatment of HIV-related HL, and data on its epidemiology in the Russian Federation is limited. The ART allows treating HIV-infected patients with lymphomas with standard chemotherapy protocols. Aim: To study epidemiology and evaluate results of the first-line therapy of HIV-related HL. Patients and Methods: This multicenter retrospective study included 46 patients with HIV-related HL who received treatment in 9 Russian centers from 2006 to 2022. The median follow-up was 15 months (1–129). Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method. Results: The median age was 37years (25–66), men - 25 (54%), women - 21 (46%). Histological variants of HL in most cases were represented by nodular sclerosis (60%) and mixed-cell subtype (37%). The advanced stage of the disease was observed in 74% of patients, B-symptoms at the onset of the disease - 65%, extranodal involvement-52%. All patients were on ART at the start of HL therapy. The median number of CD4+ cells/μl at the onset of HL was 354 (50–727). ECOG status at the start of therapy was 0–1 in 39 (84.8%), ECOG≥2 in 7 (15.2%). As the first line of therapy, patients with early stages of HL received ABVD (79,4%) and BEACOPP therapy (20,6%), with advanced stages - ABVD (58.7%) and BEACOPP-like (41.3%). The median number of first-line therapy cycles was 4 (1–10). Radiation therapy in first-line therapy was performed on 6 patients. The structure of response to first-line therapy: complete response - 81.6%, partial response - 26.3%, disease stabilization - 2.6%, disease progression – 17.9%. 2-years OS in the study group was 85%, PFS - 49% (median PFS – 23.2 months). The level of CD4+ cells at the onset of HL less than 266.5/μl was associated with a significant worsening of 2-year OS (57% vs 100%, p=0.019). Also, ECOG-status ≥2 significantly worsened 2-year OS (71% vs 88%, p=0.033). Factors such as gender, age, stage of the disease, the presence of B-symptoms and extranodal involvement at the onset of the disease, as well as the treatment regimen did not significantly affected the results of first-line therapy. Conclusion: The multicenter study allowed characterization of HIV-related HL and evaluation of the efficacy.
P074: Long-Term Cause-Specific Mortality in Hodgkin Lymphoma Patients – A Nationwide Danish Cohort Study
Authors: Sára Rossetti, Sidsel Jacobsen Juul, Frank Eriksson, Peder Emil Warming, Charlotte Glinge, Tarec Christoffer El-Galaly, Jacob Haaber Christensen, Peter Kamper, Peter De Nully Brown, Maja Vestmø Maraldo, Jacob Tfelt-Hansen, Martin Hutchings
Journal: HemaSphere (2022)

Figure 1: Aalen Johanson cumulative incidence plot demonstrating cumulative cause specific risk of death among HL patients Background: The documented treatment-induced excess mortality in Hodgkin lymphoma (HL) has resulted in important changes in treatment regimens over the last decades, aiming at maintaining efficacy with less toxic regimens. The aim of this study was to investigate whether these changes in treatment have had a long-term effect on patterns of mortality among HL patients in a nationwide unselected cohort. Methods: The study included 1,348 Danish patients aged ≤40 years at time of HL diagnosis and treated in the years 1995–2015. Cases were followed from date of diagnosis until date of emigration, death, or until study end, whichever occurred first. The primary outcome was disease specific death due to HL, with other cause specific mortality treated as competing risk. A comparison of risk of death in the study population and national background population was performed in a landmark analysis. Results: At time of diagnosis, 66.5% of patients had Ann Arbor stage I-II; 33.5% had stage III-IV disease. After a median follow-up of 13.8 years (a total of 18,731 person-years), 139 patients (10.3%) had died with a 5-year overall survival rate of 94.6% (95% CI 93.4–95.8). Among these, 71 had died due to HL, 19 due to second malignancies, and 9 due to cardiovascular disease. Cumulative risk of death due to HL had an initial steep increase mounting to 6.1% 10 years after diagnosis, whereas the risk of death due to cardiovascular, pulmonary disease or second cancers increased at 10 years after HL diagnosis, however, only to a cumulative risk of 1.2% and 2.0%, respectively, at 20 years. By 21.6 years of follow-up risk of death due to HL was exceeded by risk of death due to other causes. We found a 6.5-fold higher risk of mortality among HL cases compared to the background population. Sub-analyses on overall and cause-specific mortality risk stratified by age, sex, disease stage, treatment period and exposure, will be presented. Conclusion: Our results show a decrease in overall risk of mortality and disease-specific mortality among HL patients exposed to contemporary treatment compared to patients from earlier treatment eras. We also find a remarkable decrease in both overall and relative risk of death due to possible treatment related late-effects. So even though excess mortality among HL patients compared to the background population persists, our results suggest that the changes in treatment strategies have led to a distinct reduction in risk of fatal long-term toxicity.
P088: Case series of Nodular Lymphocyte Predominant Hodgkin Lymphoma from Tanzania. A common entity in East Africa?
Authors: Atukuzwe Kahakwa, Elifuraha Mkwizu, Alex Mremi, Priscus Mapendo, Oliver Henke
Journal: HemaSphere (2022)

Background: NLPHL is a rare subtype of HL and constitutes to approximately 5% of all HL, hence less than 0.5% of all lymphomas [1,2]. For Sub-Saharan Africa, publications about NLPHL are literally non existing. Due to the rarity of NLPHL, clinical trial data are limited, but NLPHL are generally associated with good prognosis [3,4]. Due to the CD20 positivity, the use of CD20-antibodies is recommended and contributes to a good treatment outcome according to publications from high income countries. As treatment outcome and patient’s characteristics from African NHLP patients have not been reported as of today, we therefore display patient’s characteristics, treatment outcome and follow up from a sub-cohort of Tanzanian patients enrolled in a multi-centre study in Uganda and Tanzania focusing on EBV-driven lymphoma, the AI-REAL study [5]. Methodology: An observational descriptive case series, assessing the clinical presentation, stage, treatment and results of treatment of patient recruited through the AL-REAL [5] study at Kilimanjaro Christian Medical Centre site. Results: Out of 55 children and young adults (between 3 to 30 years of age) who were diagnosed with lymphoma, 17 had HL and 6 out of these had NLPHL. Mean age was 19.5 years (range 3–28), sex ratio 1:1, 5 presented with B symptoms, 4 were in stage III and 2 in stage I. IHC for CD20 were available in 5 patients (all positive). In the first line therapy, 2 paediatric patients received ABVD and R-ABVD, the adult patients received R-CHOP (2 cases), CHOP (1), and surgery only (1). For all patients receiving chemotherapy, 6 cycles were given. 5 patients achieved CR, and 1 patient progressed on 1st (ABVD) and 2nd (R-CHOEP) line and eventually died. Treatment outcome was assessed 2 weeks after the last cycle of chemotherapy (respectively surgery) by CT scan, the cumulative survival months up to June 2022 is 90 months, ranging from 10 to 24 months after finalizing therapy. Conclusion: This case series demonstrate a high proportion of NLPHL among the study population. Further studies should evaluate the frequency of NLPHL in the Sub-Saharan setting. With 5 out of 6 patients achieving CR (1 after 2nd line), the favorable treatment outcome described in other settings can be confirmed for Tanzania.
P045: Plasma proteome profiling of cardiotoxicity in patients with Hodgkin lymphoma
Authors: Johan Mattsson Ulfstedt, Eva Freyhult, Christina Christersson, Charlott Mörth, Masood Kamali-Moghaddam, Anna Eriksson, Gunilla Enblad, Daniel Molin
Journal: HemaSphere (2022)

Introduction: Cardiovascular toxicity is a well-known complication of both chemotherapy, especially doxorubicin (DXR), and irradiation of the mediastinum for classical Hodgkin lymphoma (cHL). Due to the excellent prognosis in cHL, the mortality rate in late toxicity historically exceeds that of cHL 15 to 20 years after diagnosis, highlighting the need for strategies to minimize toxicity. Our aim was to characterize the incidence of cardiovascular disease (CVD) in our cohort of cHL patients treated with DXR with or without radiotherapy according to standard practice, and to identify any plasma protein associations with pre-existing or emerging CVD post treatment. Patients and Methods: We analyzed 182 different proteins in 58 biobanked plasma samples from cHL patients using Olink multiplexed panels. The analysis was complemented with separate analyses of NTpro-BNP, Troponin I and CRP. The patient samples were prospectively collected prior to, during and after treatment. Patient charts were reviewed for CVD and risk factors for CVD at diagnosis and after a median follow-up time of 7.8 years. In addition, plasma samples from 60 healthy controls, recruited from the EpiHealth survey, and health related data was collected from patient surveys. Results: Our analysis showed a statistically significant association between the compound endpoint of heart failure and ischemic heart disease and the protein biomarkers cysteine rich protein 61 (CYR61), glycoprotein nonmetastatic melanoma protein B (GPNMB) and activated leukocyte cell adhesion molecule (ALCAM) in samples collected after treatment for cHL. Conclusions: This study identified three possible biomarkers for cardiac damage in patients treated for cHL. We believe that optimizing treatment based on prognostic factors in this population has the potential to reduce future morbidity and mortality.
P031: CD4+ T cells in close proximity to Hodgkin-Reed Sternberg cells are antigen experienced, polyclonal and display an exhausted phenotype
Authors: Johanna Veldman, Jessica Rodrigues Plaça., Lauren Chong, Martijn Terpstra, Mirjam Mastik, Léon C. Van Kempen, Tomohiro Aoki, Christian Steidl, Anke Van Den Berg, Lydia Visser, Arjan Diepstra
Journal: HemaSphere (2022)

Figure 1: Immunohistochemistry for TOX in a representative case of Hodgkin lymphoma. TOX stains nuclei of T cells in close proximity to the tumor cells. Introduction: Little is known about the characteristics of the CD4+ T cells residing in close proximity to the tumor cells in classical Hodgkin lymphoma (cHL). We recently established that these CD4+ T cells interact with tumor cells by binding of CD2 to CD58 and T cell receptor to HLA class II in vitro and in situ. Formation of this immunological synapse results in strong T cell activation under normal conditions, but the CD4+ T cells in cHL are only weakly activated and typically lack expression of the activation marker CD26. The aim of this study was to further characterize these T cells. Methods: CD4+CD26- and CD4+CD26+ T cell subsets were sorted from 19 cHL lymph node derived cell suspensions (tumor cells HLA class II positive) and analyzed by RNA sequencing and T cell receptor variable gene segment usage. In addition, co-expression of genes of interest was investigated at the single cell level using previously generated single-cell RNA sequencing (scRNA-seq) data and at the protein level by immunohistochemistry. Results: Gene set variation analysis showed an enrichment of memory Treg, Th17 and T follicular helper cell gene signatures in CD4+CD26- T cells, while naïve and Th1/17 gene cell signatures were enriched in CD4+CD26+ T cells. Although CD4+CD26- T cells displayed an antigen experienced phenotype, the T cell receptor variable gene segment usage was polyclonal and did not differ from CD4+CD26+ T cells, indicating lack of clonal expansion. Differential gene expression analysis revealed a significant enrichment of 100 genes in CD4+CD26- T cells. Seven genes (TOX, TOX2, CXCL13, CTTN, PDCD1, CD200 and NFIA) with a moderate to high expression level were chosen for subsequent co-expression analysis using scRNA-seq data. This revealed that the majority of CD4+CD26- T cells expressed TOX2 either alone or in combination with any of the other selected genes. Protein expression of TOX and TOX2, transcription factors crucial for the acquisition of an exhausted T cell phenotype, was accentuated in T cells that physically interact with tumor cells. More than 50% of these rosetting T cells were positive for TOX in 63% and TOX2 in 79% of cHL cases. Conclusion: CD4+ T cells residing in close proximity to cHL tumor cells are polyclonal, antigen experienced and exhausted. We propose that TOX and TOX2, transcription factors known to induce expression of a variety of immune checkpoints, are attractive therapeutic targets for cHL.
T001: FDG-PET and serum TARC levels after one cycle of BV-AVD in advanced stage Hodgkin lymphoma patients: results from the very early PET-response adapted EORTC-COBRA trial
Authors: Arjan Diepstra, Lydia Visser, Catherine Fortpied, Walter Noordzij, Annika Loft, Anne Arens, Anna Sureda-Balari, Susana Carvalho, Andrej Vranovský, Ward Sents, Emanuel Buhrer, Wouter J. Plattel, Martin Hutchings
Journal: HemaSphere (2022)

Figure 1: Serum TARC levels for 96 individual patients at baseline and after one cycle of BV-AVD. The COBRA trial (EORTC-1537) is a fully enrolled, single-arm multicenter phase II study investigating the value of very early FDG-PET-response adapted Brentuximab Vedotin (BV)-based therapy for advanced stage classical Hodgkin Lymphoma (cHL). All patients received one cycle of BV, Doxorubicin, Vinblastine, and Dacarbazine (BV-AVD) followed by an early interim 18F-FDG-PET scan (iPET). Patients with a negative iPET by central assessment continued with five additional BV-AVD cycles, while iPET+ patients escalated to six cycles of BV, Etoposide, Cyclophosphamide, Doxorubicin, Dacarbazine, and Dexamethasone (BV-ECADD). The main objective of this trial is to assess whether treatment adaptation based on iPET results in improved efficacy while minimizing treatment toxicity. We here report baseline characteristics and iPET results after one cycle of BV-AVD. Deauville scores 4 or 5 were considered positive. In addition, we used ELISA to measure serum thymus and activation regulated chemokine (TARC) levels, which have been reported to reflect cHL disease activity and correspond with treatment response. TARC levels were measured both at baseline (bTARC) and after one cycle of BV-AVD (iTARC). A serum TARC level >1000 pg/ml was considered positive for detecting active disease (PMID 22058214). A total of 150 patients were included in the trial. Median age at inclusion was 32 years and 46% were females. Patients presented with stage IIB (15%), III (25%) or IV (60%) disease. Bulky disease was present in 56%. bTARC levels are currently available for 96 patients and were positive in 88 (92%), with a median level of 51831 pg/ml (range: 62–2033694). There were significant differences in bTARC levels across stages (p_value=0.044, F test), with bTARC levels lower for stage IIIA, as compared to IIB, IIIB or IV, but not with regards to bulky disease, age or gender. After one cycle of BV-AVD, iPET was positive in 40% of the patients. Within the group of patients with available iTARC and positive bTARC (n=84), iPET was positive in 33 cases (39%) and iTARC was positive in 12 cases (14%). Eight out of these 12 iTARC positive cases were also iPET positive. In conclusion, the majority of advanced stage Hodgkin patients showed a treatment response already after 1 cycle of BV-AVD, as measured by FDG-PET and serum TARC. FDG-PET quantification and tissue analysis for TARC expression are ongoing. These are preliminary data; definitive results will be presented at the symposium.
P079: PROCTCAE as a patient-reported outcome measurement (PROM) questionaire in patients with Hodgkin Lymphoma captures different adverse events profile than those reported by physicians
Authors: Sergio Ramos-Cillan, Eva Castillo, Miriam Riesco, Antonio Herroro, Adriana Pascual, Alberto Lopez-Garcia, Maria Angeles Perez, Daniel Morillo, Alham Askari, Elena Prieto, Pilar Llamas, Javier Becares, Carla Barriocanal, Marta Del Olmo, Jorge Short, Javier Arcos, Raul Córdoba
Journal: HemaSphere (2022)

Figure 1: Pareto charts show AEs reported by physicians (1a and 1c) and patients (1b and 1d) in patients with diagnosis of Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). Background and aims: Patient reported outcomes(PROs)are used in clinical trials to evaluate toxicity,effectiveness, and quality of life.A program to assess PROs was started at our hospital in2020.Here we present preliminary results about its utility in reporting symptoms and reducing visits toEmergencies and hospitalization.Patients complete a questionnaire at every cycle of treatment. Methods: Patients(pts)with diagnosis of any type of lymphoma in need of starting therapy in our hospital between 1st Jan 2019 and 31st Dec 2021 were included in our study. Pts who started treatment in 2019 and those who refused to participate in 2020 and 2021 were considered the control arm of our study. Principal endpoint was to compare physician and patient-reported adverse events through a standardized questionnaire (PRO-CTCAE). Secondary endpoints included association between inclusion in PROMs program and reduction of hospital admissions and Emergencies visits. Here, we present the preliminary results from answers given at the beginning of treatment (as it is considered the period were most toxicity is expected). A subgroup analysis to study patients with Hodgkin lymphoma(HL)was performed. Results: Two-hundred and eight patients were included.Thirty-six(17,3%)were HL.Patients with HL were significantly younger (49.3vs.63.5 y.o.;p=0,029).No differences were found in terms of adherence to PROMs program between HL and NHL(52.8%vs.56.4%; p=0,69).Figure 1 shows most commonly adverse events (AEs) reported by clinicians and patients among those with diagnosis of HL and NHL. Differences were found in both groups.Differences between patients with HL and NHL were found at sexual symptoms reported by physicians(10.5%among HL and 1%among NHL; p=0,02)and tendency to statistically significant difference at oral symptoms reported by patients(36.1% among NHL and 15.1% among HL;p=0.085). Patients included in the PROMprogram would visit Emergencies less than those in the control arm. Difference was statistically significant in the whole group(n=208)and showed tendency to significancy in the smaller group of HL(31.6%vs.58.8%;p=0,1).The same happened with unscheduled hospitalization. Conclusions: Integration of PROs is essential to evaluate the effect of treatment. Incorporation of patients’ perspective makes personalized medicine more concrete. Physicians and patients report different symptoms and intensity and those included in the program tend to use fewer unscheduled resources.